Current Pharmaceutical Biotechnology - Online First

The most prevalent kind of cancer among women is breast cancer. Consequently, the development of novel, potent medications with fewer adverse effects is required to treat it. Breast cancer is frequently treated clinically with chemotherapy and surgery. However, there are still significant challenges to be addressed in the treatment of breast cancer, including inadequate therapeutic results, inevitable side effects, and the surgical excision of breast tissue. The objective of the study is to develop broccoli extract-based Hydrogel to overcome the challenges in breast cancer treatment.

The developed Hydrogel was characterized by certain techniques to check its stability and drug release abilities. Swelling studies and drug release behavior were checked; the porosity of Hydrogel was checked by SEM EDX Analysis. Furthermore, in vitro studies were done to check the anti-breast cancer activity of the developed Hydrogel.

The hydrogel was a highly porous structure with and compressive modulus, which makes it good for biological use in drug delivery. The in vitro studies showed that, developed Hydrogel inhibits the growth of breast cancer cells (MCF-7) at different concentrations and time intervals of 24 and 48 Hrs and was compatible with the non-cancerous cell line 3T3-L1. The results indicate the tolerability of Hydrogel at the level of cells.

Numerous investigations have demonstrated the anticancer effects of SFN by influencing the various biological processes that tumor cells engage in. In breast cancer cell lines, SFN functions as an HDAC inhibitor and reduces the expression of ER, EGFR, & HER-2 proteins. SFN also triggers apoptosis and cell cycle halt. Both Hydrogel and SFN inhibit the cells growth in MCF-7 breast cancer cells and agree with the previous studies.

In conclusion, we synthesized a hydrogel using broccoli extract to treat breast cancer with better stability, tolerance, and effectiveness through sustained local drug delivery. It was determined that this new hydrogel was a simple and affordable way to accomplish the continuous gene release feature, which would enhance the therapeutic efficacy in anti-cancer treatment while reducing the likelihood of potentially fatal side effects.

In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of Astronium urundeuva (M. Allemão) Engl. has shown potential, as it is traditionally used in folk medicine for the treatment of inflammation and multiple infections. Thus, the aim of this study was to evaluate the chemical profile, anti-Candida activity, and Fluconazole (FCZ) potentiating effect of the essential oil extracted from the leaves of A. urundeuva (EOAU) and its ability to inhibit the virulence mechanism in Candida species.

The essential oil was obtained via hydrodistillation and characterized using gas chromatography-mass spectrometry. To evaluate the antifungal effects and the modulating activity of Fluconazole (FCZ), the essential oil was diluted in DMSO (1 mL) and SDB medium (9 mL) and tested on 3 Candida strains using the serial microdilution method. In addition, a morphological transition assay was used to evaluate its capacity to inhibit fungal virulence.

The major constituent of EOAU was the monoterpene β-myrcene (71.07%). The results indicate that the essential oil exhibits an antifungal effect, with C. tropicalis being the most susceptible species. At subinhibitory concentrations (MC/8), the EOAU enhanced the action of fluconazole against C. krusei and C. tropicalis. The EOAU strongly inhibited the morphological transition in C. tropicalis.

EOAU is rich in β-myrcene and exhibits an interesting fungistatic effect, making it a great natural candidate for inhibiting Candida spp. virulence.

The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation.

This study reports the synthesis of two novel CQ-derived compounds, 7-chloroquinolin-4-amine (CQC1) and 7-chloro-4-(¹-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation.

Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated.

The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ).

Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment.

The objective of this study was to evaluate the potential use of cellulose produced by acetic acid bacteria isolated from rotten fruits as a wound dressing.

In our study, rotten fruit samples were incubated in Hestrin-Schramm (HS) Broth medium. Then, a loopful of the pellicle-forming samples was taken and inoculated onto Hestrin-Schramm (HS) agar using the streak culture method and bacteria were isolated. Identification of bacteria was performed using the BLAST program after 16S rRNA sequence analysis. Physicochemical properties and morphological characterization of bacterial cellulose produced by static culture were examined using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), respectively, and the swelling ratio was investigated. Antibiotic susceptibilities of bacterial cellulose membranes impregnated with different concentrations of gentamicin (50 µg/mL, 100 µg/mL, 200 µg/mL) against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were determined by the disk diffusion method.

The bacteria isolated from rotten fruits were identified as Acetobacter tropicalis NBRC 16470. The structure of cellulose produced by static culture was confirmed by a peak at 3,240 cm⁻¹ in FTIR analysis and fibril structures in SEM analysis. Bacterial cellulose had a swelling ratio of 27.37± 2 .99 fold. The zone diameters formed by bacterial cellulose disk (50 µg/mL gentamicin) and gentamicin (10 µg) disk against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were almost the same.

The production of bacterial cellulose, which has the potential to be used as a wound dressing from rotten fruits, is important in terms of recycling and low cost.

Scientists around the world are focusing on ‘green,’ environment-friendly, and cost-effective green synthesis of nanometals using various plant extracts to combat various ailments. Among nanometals, Silver (Ag) is one of the most commercialised nano-materials due to its wide applications in biotechnology and biomedical fields. The present study reports the first facile synthesis, characterization, and process optimisation of Ag nanoparticles (NPs) using aqueous Grewia tiliaefolia leaf extract (Gt) as a reducing and surface functionalising agent.

Characterisation of Gt-mediated Ag-NPs was performed using FTIR. The morphology and microstructures of Gt-derived Ag-NPs were analysed using TEM and FE-SEM. In vitro, antioxidant activity was evaluated against DPPH radicals, hydrogen peroxide radicals, and ferric ions. In vitro, anticancer activity was assessed on MCF-7 and HepG2 cell lines. In vivo, hepatoprotective activity was tested against paracetamol-induced liver toxicity in rats.

FTIR analysis confirmed the interaction between Ag-NPs and Gt. The optimal conditions for Gt-derived Ag-NPs were found to be 4 mM AgNO3, 5% Gt, at 90°C for 60 minutes, at pH 9. UV-Visible spectroscopy, XRD, FE-SEM, and TEM revealed the phase formation, spherical morphology, and surface functionalisation of Gt-derived Ag-NPs, which were stable (-28.3 mV) with an average particle size of 14.5±0.05 nm. The Gt-derived Ag-NPs were found to be highly effective in significantly inhibiting DPPH radical, ferric ions, and hydroxyl radicals. Additionally, the cytotoxicity of Gt-derived Ag-NPs was more effective against MCF-7 cells compared to HepG2 cells. They also exhibited dose-dependent protection against hepatoprotective activity in albino rats.

The hepatoprotective effects of Gt-mediated Ag-NPs likely result from the combined action of bioactive phytochemicals (such as α/β-amyrin, γ-lactones, betulin, and lupeol), and their ability to scavenge ROS, reduce oxidative stress, and modulate inflammatory pathways. These mechanisms, supported by reduced lipid peroxidation and increased antioxidant activity in paracetamol-induced hepatotoxicity, suggest their therapeutic potential in liver protection and regeneration.

Overall, Gt proves to be an eco-friendly and non-toxic source for synthesizing bioactive Ag-NPs at optimal conditions.

The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer’s disease (AD). However, the molecular mechanisms underlying its anti-dementia effects, particularly its multi-component synergy and pathway modulation, remain poorly understood.

Our study employed an integrated systems pharmacology approach to mechanistically decode the anti-AD properties of ZZ-HQ, combining network pharmacology predictions, molecular docking simulations, and experimental validation to identify critical bioactive components, molecular targets, and therapeutic pathways.

A comprehensive network pharmacology analysis was performed to identify bioactive compounds within the ZZ-HQ complex and their potential protein targets associated with AD. Molecular docking was utilized to predict and assess the binding interactions between key bioactive compounds and AD-related protein targets. Experimental validation focused on baicalin, a major active compound in the ZZ-HQ complex, evaluating its effects on cell viability, apoptosis regulation, oxidative stress reduction, and the activation of the PI3K/Akt signaling pathway.

Fifty-four bioactive compounds were identified in the ZZ-HQ complex, interacting with 258 AD-associated proteins. Key compounds, such as baicalein and norwogonin, demonstrated strong binding affinities with pivotal proteins, including SRC and PIK3R1. Experimental studies further confirmed that baicalin significantly improved cell viability by activating the PI3K/Akt pathway, reducing apoptosis, and alleviating oxidative stress.

Our study uncovered the therapeutic potential of the ZZ-HQ combination in addressing AD through multi-target mechanisms, particularly via modulation of the PI3K/Akt pathway and oxidative stress. These findings provide a scientific basis for the pharmacological effects of ZZ-HQ and offer valuable insights for further research on its potential application in AD treatment.

Hydroxysafflor Yellow A (HSYA), known for its anti-inflammatory effects in cardiovascular diseases, has also been shown to reduce adiposity and improve metabolic disorders in diet-induced obese (DIO) mice. However, the molecular mechanisms underlying its anti-obesity effects, particularly whether they are mediated through immune-inflammatory pathways, remain unclear. This study aims to identify the key molecular mechanisms involved in HSYA's anti-obesity action.

Male C57BL/6J mice were divided into three groups: Standard Feed (SF), High-Fat Diet (HFD), and HFD with HSYA treatment (250 mg/kg/day for 9 weeks). Whole transcriptome sequencing of White Adipose Tissue (WAT) identified Differentially Expressed Genes (DEGs), which were integrated with network pharmacology predictions to identify key molecular targets of HSYA. RT-qPCR in WAT, 3T3-L1 adipocytes, and RAW264.7 macrophages validated the core genes, and molecular docking assessed HSYA’s binding affinity with these targets.

HSYA treatment significantly reduced body weight (35.27 ± 1.27g vs. 45.46 ± 1.68g, p < 0.05) and WAT mass (3.38±0.21g vs. 1.86±0.27g, p < 0.05) in DIO mice and ameliorated glucose and lipid metabolism abnormalities. Transcriptome analysis revealed 739 DEGs, with 21 overlapping genes identified between sequencing and network pharmacology analyses. Experimental validation highlighted Prkcd, Btk, and Vav1 as core genes within immune-inflammatory pathways, including chemokine and B cell receptor signaling, which are implicated in obesity-related inflammation. RT-qPCR confirmed the downregulation of Prkcd, Btk, and Vav1 after HSYA treatment, consistent with transcriptomic findings. Molecular docking analysis demonstrated strong binding affinities between HSYA and VAV1 (-8.5 kcal/mol), BTK (-6.9 kcal/mol), and PRKCD (-6.6 kcal/mol).

HSYA demonstrates the therapeutic potential for obesity by modulating immune-inflammatory pathways in WAT, specifically targeting Prkcd, Btk, and Vav1 in mice. Given its clinical use in cardiovascular disease, these findings suggest that HSYA may offer broader therapeutic benefits, including obesity management, though further studies are needed to clarify the mechanisms and assess its applicability to humans.

This study investigates causal relationships between gut microbiota (GM), plasma metabolites, and cerebral small vessel disease (CSVD), with a focus on identifying GM taxa and metabolites that mediate disease risk.

Summary data from genome-wide association studies on GM (MiBioGen), 1,400 plasma metabolites, and CSVD were analyzed using a two-step Mendelian randomization (MR) approach. The primary analysis utilized inverse-variance weighting, complemented by weighted median, weighted mode, and MR-Egger methods for robustness.

The MR analysis identified 12 GM taxa associated with CSVD risk, including 7 taxa linked to increased risk (Veillonellaceae, Hungatella, Ruminococcus2, Lachnospiraceae UCG010, Streptococcus, Cyanobacteria, Verrucomicrobia) and 5 taxa linked to decreased risk (Faecalibacterium, Alphaproteobacteria, Eubacterium nodatum group, Fusicatenibacter, Rhodospirillales). Additionally, 10 plasma metabolites were causally associated with CSVD risk, with sphingomyelin (d18:2/14:0, d18:1/14:1), nicotinamide, 3-ethylcatechol sulfate (2), sphingosine, and phenylpyruvate-to-4 hydroxyphenylpyruvate ratio linked to increased risk, while phosphate-to-uridine ratio, adenosine 5'-diphosphate (ADP)-toflavin adenine dinucleotide (FAD) ratio, arginine, caffeine-to-theobromine ratio and N-succinylphenylalanine were linked to decreased risk. Mediation analysis identified 8 causal pathways through which plasma metabolites connect GM taxa to CSVD.

These findings underscore the substantial influence of GM and plasma metabolites on CSVD risk, highlighting potential therapeutic targets. Further investigation is needed to elucidate the biological mechanisms underlying these associations.